Memory Protection

As a clinician, Lori Daiello F’08 ScM’12, PharmD, worked with countless families struggling to care for loved ones with dementia and Alzheimer’s disease. She says she’d hear things like, “‘Mom’s memory was fine until after she had that knee replacement, or that shoulder surgery.’”

Previous studies found that up to 45 percent of senior patients experience postoperative delirium (POD): temporary confusion, disorientation, and memory or attention problems during the week following surgery. Postoperative cognitive dysfunction (POCD), meanwhile, affects 5 to 55 percent of patients and may not be apparent until several months after they leave the hospital.

Although most patients with POCD will return to normal within six months of surgery, studies also showed that up to 15 percent will experience “a more serious condition that can lead to persistent problems with memory or thinking,” says Daiello, a researcher at the Rhode Island Hospital Alzheimer’s Disease and Memory Disorders Center.

“The majority of people will have good and safe outcomes following surgery,” she adds. “But the older we get, the risk of developing some type of postoperative cognitive disorder increases.”

Daiello first tried to get to the bottom of this as a research fellow and then an epidemiology graduate student at Brown in the late 2000s, when the prevailing literature claimed that anesthesia was the reason some patients’ cognitive abilities declined after surgery. But more recent research indicates it’s probably not the primary cause. “So if it isn’t anesthesia, what is it?” she wondered.

HOLE IN THE WALL

The answer may lie in the blood-brain barrier, “one of the most fascinating parts of the brain that most people have never heard of,” Daiello says.

The barrier is formed by the endothelial cells that line the tiny blood vessels surrounding the brain, which join very tightly in a nearly impenetrable junction. This “wall” is supposed to keep the brain safe by preventing noxious substances in the blood from entering its environment.

However, for reasons that are unclear, the blood vessels that form this protective structure can become damaged over time, letting in potentially harmful substances. Daiello says that in some people, the combination of a “leaky” blood-brain barrier and high concentrations of certain inflammatory proteins found in the bloodstream after surgery may be at least partly responsible for postoperative cognitive problems, by harming neurons in the aging brain.

Recent research shows that the blood-brain barrier is also leaky in some neurodegenerative diseases like Alzheimer’s, amyotrophic lateral sclerosis (ALS), epilepsy, and multiple sclerosis, as well as in traumatic brain injuries and strokes, she adds.

Now Daiello, an associate professor of neurology and of health services, policy, and practice (research) at Brown, can test the hypothesis, thanks to a five-year, $3.8 million grant from the National Institutes of Health.

Over the next five years, her research team will scan the brains of 200 people undertaking major surgery, both before and then three months after their operations. The researchers will also conduct paper-and-pencil memory tests and study inflammatory factors in blood to identify certain proteins that might provide clues to what’s going on biologically.

Anesthesia isn’t “entirely off the hook” as a possible contributor to memory loss, Daiello says. But she hopes that studying the blood-brain barrier might help scientists find ways to prevent postoperative cognitive problems in senior surgical patients.

“More older people facing major operations are questioning whether surgery intended to heal the body might harm the brain,” she says. Identifying and understanding the mechanisms behind cognitive impairment is an important first step toward finding “effective ways to protect the aging brain.”